Placental mitochondrial DNA mutational load and perinatal outcomes: Findings from a multi-ethnic pregnancy cohort

Mitochondria fuel placental activity, with mitochondrial dysfunction implicated in several perinatal complications. We investigated placental mtDNA mutational load using NextGen sequencing in relation to birthweight and gestational length among 358 mother-newborn pairs. We found that higher heteroplasmy, especially in the hypervariable displacement loop region, was associated with shorter gestational length. Results were similar among male and female pregnancies, but stronger in magnitude among females. With regard to growth, we observed that higher mutational load was associated with lower birthweight-for-gestational age (BWGA) among females, but higher BWGA among males. These findings support potential sex-differential fetal biological strategies for coping with increased heteroplasmies.